Mechanisms of metal carcinogenesis

Experimental observations that pertain to mechanisms of metal carcinogenesis are summarized, with emphasis upon (a) interactions of metals with nucleic acids in vitro; (b) impairment by metals of the fidelity of DNA replication by DNA polymerase in vitro; (c) mutagenicity of metals in microorganisms; (d) cytogenetic aberrations induced by metals in tissue culture cells; (e) induction by metals of neoplastic transformation of tissue culture cells; and (f) nuclear uptake of metals in vivo and concomitant inhibitory effects of metals on synthesis of nucleic acids. Considered in toto, the experimental data support the somatic mutation hypothesis of chemical carcinogenesis. Sufficient experimental evidence is available regarding four carcinogenic metals (As, Be, Cr, and Ni) to permit speculations about the molecular reactions whereby these metals may induce somatic mutations.